Neuropsychiatric manifestations in Cornelia de Lange syndrome

Introduction Cornelia De Lange syndrome (CdLS) is a dominant and rare genetically heterogeneous syndrome. It is characterized by a large phenotypical spectrum going from a classical to a non-classical form affecting multiple organ systems including central nervous, locomotor, skin, gastrointestinal, immune and endocrine systems in association with specific dysmorphic features. Neuropsychiatric manifestations represent a hallmark of CdLS phenotype. Objectives The aim of this study is to describe the neuropsychiatric features of Cornelia De Lange syndrome. Methods This is a descriptive and retrospective study compromising unrelated Tunisian patients diagnosed clinically and genetically with CdLS during the period between 2002-2021. Each patient underwent a comprehensive clinical evaluation. In this study, we focused on neuropsychiatric and behavioural phenotype specifying intellectual disability(ID), language delay (LD), autism spectrum disorder (ASD), hyperactivity, aggressivity, specific learning disorder(SLD), sleep problems, compulsive behaviours and social anxiety disorders during adolescence. Results A total of nine patients were included in this study. ID was present in all the evaluated patients with different level of severity evolving from mild (8/9) to severe (1/9). LD in absent of hearing problems was detected in two patients. Hyperactivity was found in three patients. Aggressivity was discovered in one patient in a form of self-injurious behaviour in one patient and hetero-aggressivity in another. None of our patients was diagnosed with ASD. Sleep problems such as frequent night-time awakenings were observed in one patient. All patients at age of schooling presented different levels of SLD. None of our patients was diagnosed with anxiety or compulsive behaviours. Conclusions Our results support the implication of behavioural and psychiatric features in CdLS phenotype. All of symptoms described in the literature were present in our patients. Further evaluation of our patients during their life is important to reveal age-related features such as anxiety or compulsive behaviours. These features can be used to inform specific psychiatric assistance for family psychoeducation, psycho-social interventions, and cognitive-behavioural education treatment approaches in individuals with CdLS. Disclosure of Interest None Declared

Introduction: Attention-deficit/hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder in children and adolescents. It is characterized by age-inappropriate inattention/ impulsiveness and/or hyperactivity symptoms. However, emotional symptoms are frequent in patients with ADHD and may, in some cases, be responsible for a major part of the negative impact on functioning and outcome. It is now well established that a large number of children with ADHD and without any comorbid disorder exhibit symptoms of emotional lability. Recently , given the importance of the impact of emotional symtoms , several authors have argued that emotional intelligence affects health and is essential for success in academics as well as life in general and it is defined as the ability to perceive, appraise, and express emotions; the ability to access and/or generate feelings when they facilitate thought; and the ability to regulate emotions to promote emotional and intellectual growth. Objectives: •Our research aimed to evaluate and compare the emotional and social functioning of two groups of children, with and without ADHD , aged 6 to 19 . Methods: •One hundred twenty child (N=60 ADHD, N = 60 Control cases) were assessed with the BarOn Emotional Quotient Inventory: Youth Version (BarOn EQ-i:YV™), providing an estimate of their underlying emotional and social intelligence. •The BarOn EQ-i:YV is specifically designed to assess the coping skills, adaptability, and well-being of children and teenagers. •Children with ADHD and control cases were compared with each other. Results: •The results showed that the Emotional Quotient (EQ) was significantly lower in the group of children with ADHD (p=0.01).
•Also, our results showed that there are statistically significant differences in intrapersonal skills (p<0.0010) Adaptability Scale (p=0.005) ; General Mood Scale (p=0.004) and positive impression (p = 0.001) of emotional intelligence between children with ADHD and control cases. Thus, the first group got lower scores than the second one in all aspects. Conclusions: •ADHD is a disorder that affects the life quality of the person who suffers from it in the personal and social areas. Therefore, the emotional intelligence study in individuals with this diagnosis is important.
•And considering the fact that abilities associated with emotional intelligence can be learned and improved, emotional intelligence can be thought as a target for therapy by individualized education for patients with ADHD who have inadequate abilities compared to the healthy population . Introduction: Cornelia De Lange syndrome (CdLS) is a dominant and rare genetically heterogeneous syndrome. It is characterized by a large phenotypical spectrum going from a classical to a nonclassical form affecting multiple organ systems including central nervous, locomotor, skin, gastrointestinal, immune and endocrine systems in association with specific dysmorphic features. Neuropsychiatric manifestations represent a hallmark of CdLS phenotype. Objectives: The aim of this study is to describe the neuropsychiatric features of Cornelia De Lange syndrome. Methods: This is a descriptive and retrospective study compromising unrelated Tunisian patients diagnosed clinically and genetically with CdLS during the period between 2002-2021. Each patient underwent a comprehensive clinical evaluation. In this study, we focused on neuropsychiatric and behavioural phenotype specifying intellectual disability(ID), language delay (LD), autism spectrum disorder (ASD), hyperactivity, aggressivity, specific learning disorder(SLD), sleep problems, compulsive behaviours and social anxiety disorders during adolescence. Results: A total of nine patients were included in this study. ID was present in all the evaluated patients with different level of severity evolving from mild (8/9) to severe (1/9). LD in absent of hearing problems was detected in two patients. Hyperactivity was found in three patients. Aggressivity was discovered in one patient in a form of self-injurious behaviour in one patient and hetero-aggressivity in another. None of our patients was diagnosed with ASD. Sleep problems such as frequent night-time awakenings were observed in one patient. All patients at age of schooling presented different levels of SLD. None of our patients was diagnosed with anxiety or compulsive behaviours. Conclusions: Our results support the implication of behavioural and psychiatric features in CdLS phenotype. All of symptoms described in the literature were present in our patients. Further evaluation of our patients during their life is important to reveal age-related features such as anxiety or compulsive behaviours. These features can be used to inform specific psychiatric assistance for family psychoeducation, psycho-social interventions, and cognitive-behavioural education treatment approaches in individuals with CdLS.

EPP0804
TRAPPC9 deficiency's implication in "secondary" autism spectrum disorders Introduction: Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder with many contributing risk genes. Multiple intellectual disability (ID) susceptibility genes have been identified in ASDs to date. The trafficking protein particle complex subunit 9 TRAPPC9 (OMIM#611966) in an autosomal recessive intellectual disability (ID) gene associated with not fully penetrant phenotype combining secondary microcephaly, dysmorphic facial features, obesity, autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). Objectives: The aim of this study is to consider TRAPPC9 deficiency in autosomal recessive ID with ASD. Methods: We present the observation of two siblings, born to Tunisian consanguineous and healthy parents, followed up for syndromic intellectual disability (ID) associated ASD and microcephaly. A clinical exome sequencing was performed to one child using a Trusight One kit of Illumina. We used sanger sequencing to validate the suspected variant for the other child and to specify the parental segregation. Results: A homozygous pathogenic variant in the TRAPPC9 (NM_001160372.4) gene, c.1414C > T (p. Arg472Ter) were identified in one child. Sanger sequencing confirmed the homozygosity profile of this variant for the other child while the parents were both heterozygous carriers. Conclusions: Repetitive behaviours, especially hand-flapping, were the mean ASD feature in our patients. The current variant is known in the Tunisian population. It is described to lead to the creation of a premature stop codon and a truncating protein causing a TRAPPC9 deficiency. The impairing neuronal NFkB signalling due to TRAPPC9 deficiency has been suggested to be implicated in ASD. Due to the profound ID seen in both patients, we suggest the classification of ASD related to TRAPPC9 deficiency as "secondary" rather than "primary". Our results support the implication of TRAPPC9 in secondary ASD and shed the light on the possibility of screening p. Arg472Ter in Tunisian patients with this form of ASD as it is a recurrent mutation in the Tunisian population. Introduction: Bipolar Disorder (BD) has been suggested to be a risk factor for development of Parkinson Disease. Psychiatric drugs used as standard treatment of BD includes many drugs that are known to induce drug-induced parkinsonism (DIP). Objectives: Clinical differentiation between PD and DIP is a clinical and scientific crucial result. It might be aided by functional neuroimaging of the dopaminergic nigrostriatal pathway. Methods: Twenty consecutive BD patients with parkinsonism were clinically assessed and underwent 123 I-ioflupane dopamine transporter SPECT. Imaging data of BD patients with pathological nigrostriatal pathway were further compared to a population of de-novo PD patients. Results: Four BD patients had abnormal scans; they had higher putaminal binding ratio and putamen-to-caudate ratios than PD patients, despite similar motor symptom burden. Conclusions: in our initial results, up to 20% of BD patients with parkinsonism might have an underlying dopaminergic deficit, which is higher than excepted in the general population. This evidences supports that BD represents a risk factor for subsequent development of neurodegenerative parkinsonism.

EPP0806
Chronic obstructive pulmonary disease and comorbid psychiatric disorders: preliminary results of an 8-year retrospective study using real data Introduction: Chronic obstructive pulmonary disease (COPD) is the third leading cause of mortality worldwide. In Portugal, it is estimated to afflict 14.2% of the population over the age of 45 and is one of the most common causes of morbidity, with a significant